tbuckley/cabot-search huggingface dataset:
Duration of protection of ancestral-strain monovalent vaccines and effectiveness of bivalent BA.1 boosters against COVID-19 hospitalisation in England: a test-negative case-control study
Authors: Freja Cordelia Møller Kirsebom, Nick Andrews, Julia Stowe, Mary Ramsay, Jamie Lopez Bernal
Journal: The Lancet Infectious Diseases (2023)

Bivalent BA.1 booster vaccines were offered to adults aged 50 years or older and clinically vulnerable people as part of the 2022 autumn COVID-19 booster vaccination programme in England. Previously, all adults in England had been offered a primary course consisting of two doses of either ChAdOx1-S or monovalent mRNA vaccine and an mRNA monovalent booster vaccine. We aimed to estimate the long-term duration of protection provided by monovalent COVID-19 vaccines, and the incremental vaccine effectiveness of bivalent BA.1 boosters.In this test-negative case-control study, cases of COVID-19 and controls aged 18 years or older were identified from national data for PCR tests done in hospital settings in England. Our analysis was restricted to people with acute respiratory infections coded in the primary diagnosis field. Data for vaccination status were extracted from the English national vaccine register and linked to COVID-19 testing data. Between June 13 and Dec 25, 2022, we estimated the vaccine effectiveness against hospitalisation of two or three or more doses of monovalent COVID-19 vaccines compared with being unvaccinated, stratified by age (18-64 years vs ≥65 years). Between Sept 5, 2022, and Feb 5, 2023, we estimated the incremental vaccine effectiveness (ie, in addition to the protection from earlier vaccines) of receiving a bivalent BA.1 booster vaccine in addition to at least two doses of a monovalent vaccine (when the last dose was at least 6 months ago) among people aged 50 years or older. Analyses were adjusted for week of test, gender, age, COVID-19 risk group, residing in a care home, being a health or social care worker, Index of Multiple Deprivation quintile, ethnicity, and recent COVID-19 positivity.Our analysis of monovalent COVID-19 vaccines included 19 841 cases and 43 410 controls. Absolute vaccine effectiveness against hospitalisation among people who had received at least three doses plateaued from 6 months after the last dose at around 50% in those aged 65 years or older and at around 30% in those aged 18-64 years. Our analyses of the effectiveness of bivalent BA.1 boosters included data for 9954 cases and 39 108 controls aged 50 years or older. Incremental vaccine effectiveness peaked at 53·0% (95% CI 47·9-57·5) 2-4 weeks after administration, before waning to 35·9% (31·4-40·1) after 10 or more weeks.Our study provides evidence that monovalent COVID-19 vaccines offer moderate long-term protection against hospitalisation in people aged 65 years or older and that the bivalent BA.1 booster vaccines were effective in preventing hospitalisation among people aged 50 years or older at a time when omicron lineages were circulating in England.None.
Differential Transcriptomic Landscapes of SARS-CoV-2 Variants in Multiple Organs from Infected Rhesus Macaques
Authors: Tingfu Du, Chunchun Gao, Shuaiyao Lu, Qianlan Liu, Yun Yang, Wenhai Yu, Wenjie Li, Yong Qiao Sun, Cong Tang, Junbin Wang, Jiahong Gao, Yong Zhang, Fangyu Luo, Ying Yang, Yun-Gui Yang, Xiaozhong Peng
Journal: Genomics Proteomics & Bioinformatics (2023)

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused the persistent coronavirus disease 2019 (COVID-19) pandemic, which has resulted in millions of deaths worldwide and brought an enormous public health and global economic burden. The recurring global wave of infections has been exacerbated by growing variants of SARS-CoV-2. In this study, the virological characteristics of the original SARS-CoV-2 strain and its variants of concern (VOCs; including Alpha, Beta, and Delta) in vitro, as well as differential transcriptomic landscapes in multiple organs (lung, right ventricle, blood, cerebral cortex, and cerebellum) from the infected rhesus macaques, were elucidated. The original strain of SARS-CoV-2 caused a stronger innate immune response in host cells, and its VOCs markedly increased the levels of subgenomic RNA s, such as N, Orf9b, Orf6, and Orf7ab, which are known as the innate immune antagonists and the inhibitors of antiviral factors. Intriguingly, the original SARS-CoV-2 strain and Alpha variant induced larger alteration of RNA abundance in tissues of rhesus monkeys than Beta and Delta variants did. Moreover, a hyperinflammatory state and active immune response were shown in the right ventricles of rhesus monkeys by the up-regulation of inflammation- and immune-related RNAs. Furthermore, peripheral blood may mediate signaling transmission among tissues to coordinate the molecular changes in the infected individuals. Collectively, these data provide insights into the pathogenesis of COVID-19 at the early stage of infection by the original SARS-CoV-2 strain and its VOCs.
Reply to: Gaudry <i>et al.</i>
Authors: Armand Mekontso Dessap, Romain Arrestier, Pierre-Antoine Billiet
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"Reply to: Renal Replacement Therapy in a World of Constraints: Lessons from the COVID-19 Pandemic." American Journal of Respiratory and Critical Care Medicine, 0(ja), pp.
Improved control of a prosthetic limb by surgically creating electro-neuromuscular constructs with implanted electrodes
Authors: Jan Zbinden, Paolo Sassu, Enzo Mastinu, Eric J. Earley, Maria Munoz-Novoa, Rickard Brånemark, Max Ortiz-Catalan
Journal: Science Translational Medicine (2023)

Remnant muscles in the residual limb after amputation are the most common source of control signals for prosthetic hands, because myoelectric signals can be generated by the user at will. However, for individuals with amputation higher up the arm, such as an above-elbow (transhumeral) amputation, insufficient muscles remain to generate myoelectric signals to enable control of the lost arm and hand joints, thus making intuitive control of wrist and finger prosthetic joints unattainable. We show that severed nerves can be divided along their fascicles and redistributed to concurrently innervate different types of muscle targets, particularly native denervated muscles and nonvascularized free muscle grafts. We engineered these neuromuscular constructs with implanted electrodes that were accessible via a permanent osseointegrated interface, allowing for bidirectional communication with the prosthesis while also providing direct skeletal attachment. We found that the transferred nerves effectively innervated their new targets as shown by a gradual increase in myoelectric signal strength. This allowed for individual flexion and extension of all five fingers of a prosthetic hand by a patient with a transhumeral amputation. Improved prosthetic function in tasks representative of daily life was also observed. This proof-of-concept study indicates that motor neural commands can be increased by creating electro-neuromuscular constructs using distributed nerve transfers to different muscle targets with implanted electrodes, enabling improved control of a limb prosthesis.
Neoadjuvant Targeted Therapy in Resectable NSCLC: Current and Future Perspectives
Authors: Jay M. Lee, Ciaran J. McNamee, Eric Toloza, Marcelo V. Negrao, Jules Lin, Elaine Shum, Amy L. Cummings, Mark G. Kris, Boris Sepesi, Ilze Bara, Nino Kurtsikidze, Katja Schulze, Celina Ngiam, Jamie E. Chaft
Journal: Journal of Thoracic Oncology (2023)

The standard of care (SoC) for medically operable patients with early-stage (stages I–IIIB) NSCLC is surgery combined with (neo)adjuvant systemic therapy for patients with stages II to IIIB disease and some stage IB or, rarely, chemoradiation (stage III disease with mediastinal lymph node metastases). Despite these treatments, metastatic recurrence is common and associated with poor survival, highlighting the need for systemic therapies that are more effective than the current SoC. After the success of targeted therapy (TT) in patients with advanced NSCLC harboring oncogenic drivers, these agents are being investigated for the perioperative (neoadjuvant and adjuvant) treatment of patients with early-stage NSCLC. Adjuvant osimertinib is the only TT approved for use in the early-stage setting, and there are no approved neoadjuvant TTs. We discuss the importance of comprehensive biomarker testing at diagnosis to identify individuals who may benefit from neoadjuvant targeted treatments and review emerging data from neoadjuvant TT trials. We also address the potential challenges for establishing neoadjuvant TTs as SoC in the early-stage setting, including the identification and validation of early response markers to guide care and accelerate drug development, and discuss safety considerations in the perioperative setting. Initial data indicate that neoadjuvant TTs are effective and well tolerated in patients with EGFR- or ALK-positive early-stage NSCLC. Data from ongoing trials will determine whether neoadjuvant targeted agents will become a new SoC for individuals with oncogene-addicted resectable NSCLC.
Identification of TMexCD-TOprJ-producing carbapenem-resistant Gram-negative bacteria from hospital sewage
Authors: Jie Zhu, Jingnan Lv, Zhichen Zhu, Tao Wang, Xiaofang Xie, Haifang Zhang, Liang Chen, Hong Du
Journal: Drug Resistance Updates (2023)

Carbapenems and tigecycline are crucial antimicrobials for the treatment of gram-negative bacteria infections. Recently, a novel resistance-nodulation-division (RND) efflux pump gene cluster, tmexCD-toprJ, which confers resistance to tigecycline, has been discovered in animals and clinical isolates. It was reported that hospital sewage could act as a reservoir for gram-negative bacteria with high antimicrobial resistance genes. In this study, we analyzed 84 isolates of carbapenem-resistant gram-negative bacteria (CR-GNB) from hospital sewage, and identified five isolates of TMexCD-ToprJ-producing CR-GNB, including one Raoultella ornithinolytica isolate and four Pseudomonas spp. isolates. All these five isolates carried at least one carbapenem resistance gene and were resistant to multiple antibiotics. Multiple tmexCD-toprJ clusters were detected, including tmexC2D2-toprJ2, tmexC3D3-toprJ3, tmexC3.2D3.3-toprJ1b and tmexC3.2D3-toprJ1b. Among these clusters, the genetic construct of tmexC3.2D3-toprJ1b showed 2-fold higher minimum inhibitory concentration (MIC) of tigecycline than other three variants. In addition, it was found that the tmexCD-toprJ gene cluster was originated from Pseudomonas spp. and mainly located on Tn6855 variants inserted in the same umuC-like genes on chromosomes and plasmids. This unit co-localized with blaIMP or blaVIM on IncHI5-, IncpJBCL41- and IncpSTY-type plasmids in the five isolates of TMCR-GNB. The IncHI5- and IncpSTY-type plasmids had the ability to conjugal transfer to E. coli J53 and P. aeruginosa PAO1, highlighting the potential risk of transfer of tmexCD-toprJ from Pseudomonas spp. to Enterobacterales. Importantly, genomic analysis showed that similar tmexCD-toprJ-harboring IncHI5 plasmids were also detected in human samples, suggesting transmission between environmental and human sectors. The emergence of TMCR-GNB from hospital sewage underscores the need for ongoing surveillance of antimicrobial resistance genes, particularly the novel resistance genes such as the tmexCD-toprJ gene clusters in the wastewater environment.
Trends in HIV testing, the treatment cascade, and HIV incidence among men who have sex with men in Africa: a systematic review and meta-analysis
Authors: James Stannah, Nirali Soni, Jin Keng Stephen Lam, Katia Giguère, Kate M Mitchell, Nadine Kronfli, Joseph Larmarange, Raoul Moh, Marcellin Nouaman, Gérard Menan Kouamé, Marie-Claude Boily, Mathieu Maheu-Giroux
Journal: The Lancet HIV (2023)

Gay, bisexual, and other men who have sex with men (MSM) are disproportionately affected by HIV. In Africa, MSM face structural barriers to HIV prevention and treatment that increase their vulnerability to HIV acquisition and transmission, and undermine the HIV response. In this systematic review, we aimed to explore progress towards increases in HIV testing, improving engagement in the HIV treatment cascade, and HIV incidence reductions among MSM in Africa.
Nanocellulose-based porous materials: Regulation and pathway to commercialization in regenerative medicine
Authors: Filipe V. Ferreira, Alana G. Souza, Rubina Ajdary, Lucas P. de Souza, João H. Lopes, Daniel S. Correa, Gilberto Siqueira, Hernane S. Barud, Derval dos S. Rosa, Luiz H.C. Mattoso, Orlando J. Rojas
Journal: Bioactive Materials (2023)

We review the recent progress that have led to the development of porous materials based on cellulose nanostructures found in plants and other resources. In light of the properties that emerge from the chemistry, shape and structural control, we discuss some of the most promising uses of a plant-based material, nanocellulose, in regenerative medicine. Following a brief discussion about the fundamental aspects of self-assembly of nanocellulose precursors, we review the key strategies needed for material synthesis and to adjust the architecture of the materials (using three-dimensional printing, freeze-casted porous materials, and electrospinning) according to their uses in tissue engineering, artificial organs, controlled drug delivery and wound healing systems, among others. For this purpose, we map the structure–property–function relationships of nanocellulose-based porous materials and examine the course of actions that are required to translate innovation from the laboratory to industry. Such efforts require attention to regulatory aspects and market pull. Finally, the key challenges and opportunities in this nascent field are critically reviewed.
Advances in long-acting slow effective release antiretroviral therapies for treatment and prevention of HIV infection
Authors: Mohammad Ullah Nayan, Brady Sillman, Mahmudul Hasan, Suyash Deodhar, Srijanee Das, Ashrafi Sultana, Nam Thai Hoang Le, Vicente Soriano, Benson Edagwa, Howard E. Gendelman
Journal: Advanced Drug Delivery Reviews (2023)

Adherence to daily oral antiretroviral therapy (ART) is a barrier to both treatment and prevention of human immunodeficiency virus (HIV) infection. To overcome limitations of life-long daily regimen adherence, long-acting (LA) injectable antiretroviral (ARV) drugs, nanoformulations, implants, vaginal rings, microarray patches, and ultra-long-acting (ULA) prodrugs are now available or in development. These medicines enable persons who are or at risk for HIV infection to be treated with simplified ART regimens. First-generation LA cabotegravir, rilpivirine, and lenacapavir injectables and a dapivirine vaginal ring are now in use. However, each remains limited by existing dosing intervals, ease of administration, or difficulties in finding drug partners. ULA ART regimens provide an answer, but to date, such next-generation formulations remain in development. Establishing the niche will require affirmation of extended dosing, improved access, reduced injection volumes, improved pharmacokinetic profiles, selections of combination treatments, and synchronization of healthcare support. Based on such needs, this review highlights recent pharmacological advances and a future treatment perspective. While first-generation LA ARTs are available for HIV care, they remain far from ideal in meeting patient needs. ULA medicines, now in advanced preclinical development, may close gaps toward broader usage and treatment options.
Characteristics and complications of anogenital infantile hemangiomas: A multicenter retrospective analysis
Authors: Justin D. Arnold, SunJung Yoon, Nidhi Shah, Morgan Byrne, Lukas Kieswetter, Cathryn Sibbald, Irene Lara-Corrales, Neha Kinariwalla, Maria C. Garzon, Mitchell Braun, Sonal D. Shah, Ilona J. Frieden, Nicole Travis, Carmen Liy Wong, Alan N. Snyder, Lara Wine Lee, Erin K. Collier, Marcia Hogeling, Esteban Fernandez Faith, Nicole DeVaul, Anna Yasmine Kirkorian
Journal: Journal of the American Academy of Dermatology (2023)
Protein ligand and nanotopography separately drive the phenotype of mouse embryonic stem cells
Authors: Sadegh Ghorbani, Annette Christine Füchtbauer, Andreas Møllebjerg, Pia Møller Martensen, Sara Hvidbjerg Laursen, David Christian Evar Kraft, Jørgen Kjems, Rikke Louise Meyer, Karim Rahimi, Morten Foss, Ernst-Martin Füchtbauer, Duncan S. Sutherland
Journal: Biomaterials (2023)

Biochemical and biomechanical signals regulate stem cell function in the niche environments in vivo. Current in vitro culture of mouse embryonic stem cells (mESC) uses laminin (LN-511) to provide mimetic biochemical signaling (LN-521 for human systems) to maintain stemness. Alternative approaches propose topographical cues to provide biomechanical cues, however combined biochemical and topographic cues may better mimic the in vivo environment, but are largely unexplored for in vitro stem cell expansion. In this study, we directly compare in vitro signals from LN-511 and/or topographic cues to maintain stemness, using systematically-varied submicron pillar patterns or flat surfaces with or without preadsorbed LN-511. The adhesion of cells, colony formation, expression of the pluripotency marker,octamer-binding transcription factor 4 (Oct4), and transcriptome profiling were characterized. We observed that either biochemical or topographic signals could maintain stemness of mESCs in feeder-free conditions, indicated by high-level Oct4 and gene profiling by RNAseq. The combination of LN-511 with nanotopography reduced colony growth, while maintaining stemness markers, shifted the cellular phenotype indicating that the integration of biochemical and topographic signals is antagonistic. Overall, significantly faster (up to 2.5 times) colony growth was observed at nanotopographies without LN-511, suggesting for improved ESC expansion.
Safety of Testosterone-Replacement Therapy in Older Men
Authors: Eric Orwoll
Journal: New England Journal of Medicine (2023)

Circulating levels of testosterone decline with age in men,1 and some clinical consequences of hypogonadism resemble those of normal aging: fatigue, weakness, and impaired sexual function. These outcomes have led to the reasonable hypothesis that age-related decreases in testosterone levels may cause these symptoms and that quality of life could be improved by testosterone supplementation. Although the number of older men with testosterone levels below the normal range is small,2 the past several decades have seen large increases in the number of prescriptions for testosterone, mainly for middle-aged and older men.3 Despite the large number of men receiving testosterone supplementation, . . .
Case 21-2023: A 61-Year-Old Man with Eyelid Swelling
Authors: Natalie Wolkow, Laura V. Romo, Camille V. Edwards, Anna M. Stagner
Journal: New England Journal of Medicine (2023)

A 61-year-old man was evaluated because of eyelid swelling. Supraduction and abduction were limited, and the globes were resistant to retropulsion. A diagnostic procedure was performed.
Ultra-low tidal volume ventilation for COVID-19-related ARDS in France (VT4COVID): a multicentre, open-label, parallel-group, randomised trial
Authors: Jean-Christophe Richard, Nicolas Terzi, Hodane Yonis, Fatima Chorfa, Florent Wallet, Claire Dupuis, Laurent Argaud, Bertrand Delannoy, Guillaume Thiery, Christian Pommier, Paul Abraham, Michel Muller, Florian Sigaud, Guillaume Rigault, Emilie Joffredo, Mehdi Mezidi, Bertrand Souweine, Loredana Baboi, Hassan Serrier, Muriel Rabilloud, Laurent Bitker, Gaël BOURDIN, Emmanuel VIVIER, Audrey LARGE, Pierre DONZE, Radhia BOUZGARROU, Sophie PERINEL RAGEY, Caroline CHAUDIER, Olivier DESEBBE, Laure FOLLIET, Louis CHAUVELOT, Paul CHABERT, Guillaume DAVID, William DANJOU, Clotilde BETTINGER, Pauline BERNON, Francois DHELFT, Martin COUR, Marie SIMON, Thomas BAUDRY, Thomas RIMMELE, Jean-François CARABALONA, Arnaud GREGOIRE, Arnaud FRIGGERI, Donatien DE-MARIGNAN, Sylvain ROCHE
Journal: The Lancet Respiratory Medicine (2023)
Mucosal IgA protects against BQ.1 and BQ.1.1 infection
Authors: Ulrika Marking, Oscar Bladh, Sebastian Havervall, Nina Greilert-Norin, Max Gordon, Jessica J Alm, Kim Blom, Mikael Åberg, Jonas Klingström, Charlotte Thålin
Journal: The Lancet Infectious Diseases (2023)
Cancer Cachexia: ASCO Guideline Rapid Recommendation Update
Authors: Eric J. Roeland, Kari Bohlke, Vickie E. Baracos, Thomas J. Smith, Charles L. Loprinzi, Eduardo Bruera, Egidio del Fabbro, Suzanne Dixon, Marie Fallon, Jørn Herrstedt, Harold Lau, Mary Platek, Hope S. Rugo, Winston Tan
Journal: Journal of Clinical Oncology (2023)

ASCO Rapid Recommendations Updates highlight revisions to select ASCO guideline recommendations as a response to the emergence of new and practice-changing data. The rapid updates are supported by an evidence review and follow the guideline development processes outlined in theASCO Guideline Methodology Manual. The goal of these articles is to disseminate updated recommendations, in a timely manner, to better inform health practitioners and the public on the best available cancer care options. See the Appendix for disclaimers and other important information (Appendix 1 and Appendix 2, online only).
Long-Term Effects of Sotatercept on Right Ventricular Function
Authors: Mardi Gomberg-Maitland, Vallerie V. McLaughlin, David B. Badesch, Hossein-Ardeschir Ghofrani, Marius M. Hoeper, Marc Humbert, Ioana R. Preston, Rogerio Souza, Aaron B. Waxman, Janethe de Oliveira Pena, Jonathan T. Lu, Solaiappan Manimaran, J. Simon R. Gibbs
Journal: JACC Heart Failure (2023)
Insights into dengue immunity from vaccine trials
Authors: Eng Eong Ooi, Shirin Kalimuddin
Journal: Science Translational Medicine (2023)

The quest for an effective dengue vaccine has culminated in two approved vaccines and another that has completed phase 3 clinical trials. However, shortcomings exist in each, suggesting that the knowledge on dengue immunity used to develop these vaccines was incomplete. Vaccine trial findings could refine our understanding of dengue immunity, because these are experimentally derived, placebo-controlled data. Results from these trials suggest that neutralizing antibody titers alone are insufficient to inform protection against symptomatic infection, implicating a role for cellular immunity in protection. These findings have relevance for both future dengue vaccine development and application of current vaccines for maximal public health benefit.